CN110234334B - Muscle atrophy inhibiting composition - Google Patents
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- CN110234334B CN110234334B CN201780084998.XA CN201780084998A CN110234334B CN 110234334 B CN110234334 B CN 110234334B CN 201780084998 A CN201780084998 A CN 201780084998A CN 110234334 B CN110234334 B CN 110234334B
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- A—HUMAN NECESSITIES
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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- Engineering & Computer Science (AREA)
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- Veterinary Medicine (AREA)
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- Gastroenterology & Hepatology (AREA)
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- Orthopedic Medicine & Surgery (AREA)
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- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The present invention provides a muscle atrophy inhibiting composition comprising, as an active ingredient, a peptide selected from one or more of the group consisting of tripeptides of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK, the group consisting of dipeptides comprising F, and the group consisting of dipeptides of DI, IY, YN, and NP.
Description
Technical Field
The present application claims priority based on japanese patent application 2016-236099, the entire contents of which are hereby incorporated by reference into the present specification.
The present invention relates to a muscle atrophy inhibiting composition containing a dipeptide or tripeptide as an active ingredient.
Background
It is reported that, in humans, the muscle mass decreases by about 5% every 10 years when it is over 30 years old, and the rate of decrease of the muscle mass accelerates when it is over 60 years old. Regarding atrophy of skeletal muscle, in addition to sarcopenia (sarcopenia) which is seen in aging, it occurs due to inactivity (disuse), bed rest (bed rest), gypsum fixation) or gravity-free (outer space), denervation (denervation), diseases (cancer, AIDS), diabetes, etc., malnutrition. The phenomenon that occurs in all muscle atrophy is muscle fiber atrophy (decrease in muscle cross-sectional area) caused by decrease in muscle protein due to imbalance in synthesis and decomposition of muscle protein.
ADL (activities of daily living) or QOL (quality of life) is reduced due to muscular atrophy, and there is an increased risk of injury caused by falling, and depending on the situation, the body is prevented from standing upright and lying down for a long time. Further, since the basal metabolic rate decreases due to the decrease in the muscle mass, there is a high possibility of the occurrence of metabolic syndrome, and suppression of the decrease in the muscle mass is a major problem for the entire national population.
For prevention or improvement of muscle diseases such as sarcopenia, intensive exercise resistance training (resistance training) has been confirmed to be effective. However, for elderly people and post-illness nursing lives, the physical burden of positively performing high-intensity exercise is great, and an expert is required to perform appropriate instruction when performing high-intensity exercise. Therefore, for the prevention or improvement of sarcopenia, a method from the aspect of nutrition that can be easily performed even by a person with low basic physical strength or exercise function is desired.
As components having a muscle function improving effect expected to be effective for preventing or improving muscle diseases such as sarcopenia, there are reported a muscle atrophy inhibitor containing procyanidins as an active ingredient (patent document 1), a muscle fiber type conversion inhibitor containing fruit-derived polyphenols as an active ingredient for inhibiting conversion of muscle fiber types at the time of disuse muscle atrophy (patent document 2), a muscle function decline inhibitor containing catechins as an active ingredient (patent document 3), and the like. In addition, studies have been conducted on prevention of skeletal muscle atrophy or early recovery by ingestion of proteins or amino acids. However, no muscular dystrophy inhibiting effect associated with specific di-or tripeptides has been reported.
Prior art literature
Patent literature
Patent document 1: japanese patent laid-open No. 2002-338464
Patent document 2: japanese patent laid-open No. 2006-328031
Patent document 3: japanese patent laid-open No. 2008-13473
Disclosure of Invention
Problems to be solved by the invention
The present invention aims to provide a composition capable of inhibiting muscular dystrophy.
Technical means for solving the problems
Disclosed is a muscle atrophy inhibiting composition which contains, as an active ingredient, at least 1 peptide selected from the group consisting of tripeptides consisting of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK, the group consisting of F-containing dipeptides, and the group consisting of DI, IY, YN and NP.
ADVANTAGEOUS EFFECTS OF INVENTION
The composition of the present invention is useful for inhibiting muscular atrophy, even muscular atrophy, preventing or treating a disease accompanied by muscular atrophy such as sarcopenia or disuse muscular atrophy, and improving the decrease in muscular strength or the decrease in muscle strength or improving urination.
Drawings
FIG. 1 shows the muscle atrophy inhibition by di-and tripeptides in a mouse skeletal muscle cell line. A is the result of 17 peptides, and B is the result of additional experiments on FN and NP. Cont: control, dex: dexamethasone (Dexamethasone). * p <0.05 (relative to dexamethasone).
FIG. 2 shows the effect of FN and LR (added at 100 nM) on muscle atrophy in a mouse skeletal muscle cell line. Cont: control, dex: dexamethasone. * p <0.05 (relative to dexamethasone).
FIG. 3 is a graph showing the muscle wasting inhibition of dipeptides in model animals. Cont: control, dex: dexamethasone. * p <0.05 (relative to dexamethasone).
FIG. 4 is a graph showing the effect of a dipeptide on the expression of Atrogin-1 in a model animal. CONT: control, dex: dexamethasone. * p <0.05 (relative to dexamethasone).
Detailed Description
In the present specification, when amino acid residues are represented by abbreviations, the abbreviations are described as follows.
Ala or A: alanine residue
Arg or R: arginine residues
Asn or N: asparagine residues
Asp or D: aspartic acid residues
Cys or C: cysteine residue
Gln or Q: glutamine residue
Glu or E: glutamic acid residue
Gly or G: glycine residues
His or H: histidine residues
Lie or I: isoleucine residues
Leu or L: leucine residue
Lys or K: lysine residues
Met or M: methionine residue
Phe or F: phenylalanine residue
Pro or P: proline residues
Ser or S: serine residue
Thr or T: threonine residues
Trp or W: tryptophan residues
Tyr or Y: tyrosine residues
Val or V: valine residue
The term "peptide" in the present specification is a generic term for peptides including dipeptides, tripeptides, and longer peptides (having 4 or more amino acid residues) than tripeptides, and may refer to any of these depending on the context.
The muscle atrophy inhibiting composition of the present invention contains, as active ingredients, at least 1 peptide selected from the group consisting of a tripeptide of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK, a dipeptide including F, and a dipeptide including DI, IY, YN, and NP.
In one embodiment, the above 1 or more peptides are selected from the group consisting of F-containing dipeptides. That is, in this example, the muscular dystrophy-inhibiting composition of the present invention contains 1 or more peptides selected from the group consisting of dipeptides containing F as an active ingredient. Here, the "dipeptide containing F" is a dipeptide in which one of amino acid residues constituting the dipeptide is phenylalanine (F), and specifically, examples thereof include: FA. FR, FN, FD, FC, FQ, FE, FG, FH, FI, FL, FK, FM, FF, FP, FS, FT, FW, FY, FV, AF, RF, NF, DF, CF, QF, EF, GF, HF, IF, LF, KF, MF, PF, SF, TF, WF, YF, and VF. Among them, FN is preferable.
In one embodiment, the 1 or more peptides are selected from the group consisting of a tripeptide of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK, and a dipeptide of DI, DF, IF, FN, FY, IY, YN and NP. That is, in this example, the muscle wasting-inhibiting composition of the present invention contains 1 or more peptides selected from the group consisting of tripeptides of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK and a dipeptide of DI, DF, IF, FN, FY, IY, YN and NP as an active ingredient.
The composition of the present invention may contain 1 peptide selected from the group consisting of the above tripeptides and/or dipeptides, and may further contain 2 or more peptides. In the case where the composition of the present invention contains 2 or more peptides, these may be contained in a single formulation, or may be contained in separate formulations, respectively. In the case of separate formulations, the dosage form and route of administration of each formulation may be the same or may be different.
In one embodiment, the composition of the present invention contains only 1 or more peptides selected from the group of tripeptides and/or dipeptides as an active ingredient (i.e., contains no active ingredient other than the above). In another embodiment, the composition of the present invention comprises only 1 peptide (e.g., FN or DF) selected from the group of tripeptides and/or dipeptides described above as an active ingredient (i.e., does not comprise active ingredients other than them).
The dipeptides and tripeptides may be produced by methods generally used in the art, such as fermentation, enzyme treatment, and chemical synthesis. For example, the polypeptide can be obtained by hydrolyzing a protein or peptide containing the amino acid sequence of the target peptide with an appropriate protease, and performing separation and purification using column chromatography or the like. Alternatively, the peptide may be synthesized by Peptide Synthesis [ peptide synthesis ], interscience press, new york, 1966; the Proteins [ Proteins ], volume 2, academic Press Inc [ academic press ], new york, 1976; is a peptide synthesis, a pill (corporation), 1975; the experimental part of the synthetic fused substance [ peptide synthesis basis and experiment ], the pill (corporation) 1985; the peptide synthesis method described in U.S. Pat. No. 14, U.S. Pat. No. 5, U.S. Pat. No. 1, etc. was used for the synthesis of the peptide.
Muscle atrophy refers to muscle wasting, resulting in a decrease in muscle mass. Thus, the composition of the present invention may also be referred to as a muscle-mass-decline-suppressing composition or a muscle-strength-decline-suppressing composition. The composition of the present invention is useful for preventing or treating or improving muscular atrophy or decrease in muscle mass, and can be used for all subjects in need of preventing or treating or improving muscular atrophy or decrease in muscle mass, or desiring to prevent or treat or improve muscular atrophy or decrease in muscle mass.
In one embodiment, the composition of the invention is for use in the prevention or treatment of a disease associated with muscle atrophy. Examples of the diseases include: sarcopenia, disuse muscular atrophy, muscular dystrophy, diabetic muscular atrophy, cachexia, steroid myopathy, drug-induced myopathy, rhabdomyolysis, myasthenia gravis, amyotrophic lateral sclerosis, charcot-Marie-Tooth disease, stress urinary incontinence, etc.
In another embodiment, the composition of the invention is for improving muscle atrophy, even improving muscle mass decline or improving muscle strength decline. For example, there may be mentioned: maintaining muscle that ages with age, improving urination, etc.
In one embodiment, the composition of the invention is for use as a pharmaceutical or quasi-pharmaceutical for human or animal use. The pharmaceutical or quasi-pharmaceutical product may contain, in addition to the above-mentioned peptide as an active ingredient, a pharmaceutically acceptable carrier and/or additive (e.g., stabilizer, preservative, co-solvent, pH adjuster, thickener, antioxidant, coloring material, flavor, artificial sweetener, etc.).
The pharmaceutical or quasi-pharmaceutical product may be administered by the enteral route, or may be administered by the parenteral route. Examples of the enteral route include oral and tube feeding (tube feeding). As parenteral routes, examples may be given of: transnasal, pulmonary, intravenous, percutaneous, intramuscular, and the like.
The pharmaceutical or quasi-pharmaceutical may be appropriately formulated into a desired dosage form according to an administration method such as oral administration or non-oral administration. The dosage form of the drug or quasi-drug is not particularly limited, and in the case of oral administration, the drug or quasi-drug may be formulated into, for example, solid preparations such as powders, granules, lozenges, buccal preparations, and capsules; solutions, syrups, suspensions, emulsions and the like. In the case of parenteral administration, for example, suppositories, sprays, inhalants, ointments, patches, injections (including infusion solutions) and the like can be formulated. The composition of the present invention may be a lyophilized preparation which is dissolved by adding sterile water or the like at the time of use. Furthermore, the preparation may be carried out by a suitable known method depending on the dosage form.
The daily administration amount or intake amount of the dipeptide or tripeptide contained in the composition of the present invention is appropriately changed depending on the age, weight, symptoms, administration route, etc. of the subject, and for example, 50mg to 20g, preferably 70mg to 5g, and more preferably 100mg to 3g of each peptide. With respect to the 1-day amount of peptide, it may be administered or ingested 1 time, or may be administered or ingested in fractions. The composition of the present invention may be administered or ingested continuously or every several days, and the period is not particularly limited.
The present invention provides the following, for example.
1. A muscle atrophy inhibiting composition comprising, as active ingredients, at least 1 peptide selected from the group consisting of a tripeptide consisting of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK, a dipeptide comprising F, and a dipeptide comprising DI, IY, YN, and NP.
2. The composition according to the above 1, wherein 1 or more peptides are selected from the group consisting of dipeptides comprising F.
3. The composition according to the above 1, wherein the at least 1 peptide is selected from the group consisting of a tripeptide of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK and a dipeptide of DI, DF, IF, FN, FY, IY, YN and NP.
4. The composition according to any one of 1 to 3, wherein 1 or more peptides comprise FN.
5. The composition according to any one of 1 to 4, wherein 1 or more peptides comprise DF.
6. The composition according to any one of 1 to 5, which is used for preventing or treating a disease accompanied with muscular dystrophy.
7. The composition according to the above 6, wherein the disease is sarcopenia, disuse muscular dystrophy, diabetic muscular dystrophy, cachexia, steroid myopathy, drug-induced myopathy, rhabdomyolysis, myasthenia gravis, amyotrophic lateral sclerosis, crohn-Mary-Du Sishi disease, or stress urinary incontinence.
8. The composition according to any one of 1 to 7, which is a pharmaceutical product.
9. A composition for improving muscle mass decline, which contains, as active ingredients, at least 1 peptide selected from the group consisting of tripeptides of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK, the group consisting of dipeptides comprising F, and the group consisting of dipeptides of DI, IY, YN and NP.
10. The composition according to 9 above, wherein 1 or more peptides are selected from the group consisting of F-containing dipeptides.
11. The composition according to 9 above, wherein the at least 1 peptide is selected from the group consisting of a tripeptide of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK and a dipeptide of DI, DF, IF, FN, FY, IY, YN and NP.
12. The composition according to any one of 9 to 11, wherein 1 or more peptides comprise FN.
13. The composition according to any one of 9 to 11, wherein 1 or more peptides comprise DF.
14. The composition according to any one of 9 to 13, which is for stress incontinence improvement.
15. The composition according to any one of 9 to 13, which is for improving urination.
17. A therapeutic or non-therapeutic method of inhibiting muscle atrophy or ameliorating a decrease in muscle mass comprising administering to a subject in need thereof 1 or more peptides selected from the group consisting of a tripeptide of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK, a dipeptide comprising F, and a dipeptide of DI, IY, YN, and NP.
18. Use of a peptide selected from the group consisting of a tripeptide of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK, a dipeptide including F, and a dipeptide including DI, IY, YN, and NP for producing a muscle atrophy-suppressing composition or a muscle-mass-decreasing-improving composition, wherein the peptide is 1 or more peptides.
19. A therapeutic or non-therapeutic use of a peptide selected from the group consisting of a tripeptide of DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP and NPK, a dipeptide comprising F, and a dipeptide comprising DI, IY, YN, and NP for inhibiting muscle atrophy or ameliorating muscle mass decline.
The invention is further illustrated by the following examples, which are not intended to limit the invention in any way.
Example 1
Muscle atrophy inhibition in mouse skeletal muscle cell lines
Mouse skeletal muscle cell line (C2C 12) was treated with 10% FBS-added DMEM at 37deg.C and 5% CO 2 Subculturing and maintaining under the condition. Common medium was obtained by adding 12.5mL of HEPES (4-hydroxyethyl piperazine ethane sulfonic acid) (gibco), 5.5mL of penicillin-streptomycin (gibco) and 55mL of fetal bovine serum (FBS, sigma-Aldrich) to 500mL of DMEM (Sigma-Aldrich). The differentiation medium was obtained by adding 12.5mL of HEPES, 5.5mL of penicillin-streptomycin, and 12.5mL of bovine serum (HS, SAFC Bioscience) to DMEM.
C2C12 at 5X 10 5 Cells/dish were inoculated into 6cm dishes (Asahi Techno Glass Corporation) and cultured in ordinary medium for 2 days. Thereafter, differentiation induction is performed in a differentiation medium. After 5 days from the initiation of induction, the medium was changed to a medium to which each peptide was added (17 kinds of peptides (DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP, NPK, DI, DF, IF, FN, FY, IY, YN: medical biology institute, co., ltd.)]) 625nM, and treated for 1 hour. Thereafter, the medium was changed to include 625nM of each peptide and dexamethasone (Dex) (and photo-pure Utility industry]) 10. Mu.M differentiation medium was changed every 24 hours until 3 days later. Muscle diameters were obtained by photographing myotube cells of each group using BZ-9000 (KEYENCE) and digitizing using BZ-II image analysis application software (KEYENCE). Further, the muscle diameter was set to 100% on day 3 of the control group (no dexamethasone added), and the results are shown as percentages. Similarly, additional experiments were performed on FN and NP. Further, for FN and LR (random dipeptide), the muscle diameter was measured at an additive concentration of 100 nM.
The muscle diameter showed significantly higher values for the tripeptides or dipeptides of 17 (DIY, IYN, YNP, NPQ, DFY, DIF, FYN, IFN, FNP, NPK, DI, DF, IF, FN, IY, YN, and NP) compared to the dexamethasone-added group, and the trend difference for the FY of 1 (fig. 1, a and B). Studies were performed at an additive concentration of 100nM, with the result that FN showed significantly higher values of muscle diameter compared to dexamethasone-added group, but no significant difference in LR (fig. 2).
Example 2
Muscle atrophy inhibition in model animals
C57BL/6J mice (males, 7 weeks old) were divided into 4 groups (control, atrophic, atrophic+fn, atrophic+df) in a weight-equivalent manner. The control group and the atrophy group were allowed to freely ingest sterilized water using a water bottle for 14 days, and the atrophy+FN group and the atrophy+DF group were allowed to freely ingest an aqueous solution (1.4 mg/ml) containing each peptide using a water bottle for 14 days. Regarding the atrophic groups, the atrophic +FN group and the atrophic +DF group, dexamethasone (Sigma-Aldrich) was intraperitoneally administered at 10mg/kg 1 time 1 day after day 8 of free drinking, to induce muscle atrophy. 7 days after dexamethasone administration, it was fasted for 12 hours and thereafter used for dissection. The tibialis anterior muscle of both feet was harvested under isoflurane anesthesia, and the myofiber cross-sectional area (CSA) of the tibialis anterior muscle and the expression of Atrogin-1, a marker protein associated with muscle atrophy, were measured.
Regarding CSA of tibialis anterior, the atrophy+fn group and the atrophy+df group showed significantly higher values compared to the atrophy group (fig. 3). In addition, regarding protein expression of Atrogin-1 in tibialis anterior, the atrophic+fn group showed a lower tendency than the atrophic group, and the atrophic+df group showed a significantly lower value than the atrophic group (fig. 4).
Since the effect was confirmed in each of examples 1 and 2, it was suggested that the dipeptide containing phenylalanine (F) was effective for inhibiting muscular dystrophy. Particularly, the effects against muscle diameter and CSA are those directly showing muscular dystrophy inhibition, and as a result FN shows significant improvement and shows significant effects.
Claims (15)
1. Use of 1 or more peptides selected from the group consisting of tripeptides of DFY, DIF, FYN, IFN and FNP, and dipeptides of DF, IF, and FN, for the manufacture of a muscle atrophy inhibiting composition.
2. The use of claim 1, wherein more than 1 peptide is selected from the group consisting of DF, IF, and FN bipeptides.
3. The use of claim 1, wherein more than 1 peptide is selected from the group consisting of DF and FN bipeptides.
4. The use of claim 1, wherein more than 1 peptide comprises FN.
5. The use according to any one of claims 1 to 4, wherein the composition is for the prevention or treatment of a disease associated with muscle atrophy.
6. The use of claim 5, wherein the disease is sarcopenia, disuse muscular atrophy, muscular dystrophy, diabetic muscular atrophy, cachexia, steroid myopathy, drug induced myopathy, rhabdomyolysis, myasthenia gravis, amyotrophic lateral sclerosis, coing-mary-Du Sishi, or stress urinary incontinence.
7. The use of any one of claims 1 to 4, wherein the composition is a pharmaceutical product.
8. The use of claim 5, wherein the composition is a pharmaceutical product.
9. The use of claim 6, wherein the composition is a pharmaceutical product.
10. Use of 1 or more peptides selected from the group consisting of tripeptides of DFY, DIF, FYN, IFN and FNP and dipeptides of DF, IF and FN for producing a composition for improving a decrease in muscle mass.
11. The use of claim 10, wherein more than 1 peptide is selected from the group consisting of DF, IF, and FN bipeptides.
12. The use of claim 10, wherein more than 1 peptide is selected from the group consisting of DF and FN bipeptides.
13. The use of claim 10, wherein more than 1 peptide comprises FN.
14. The use according to any one of claims 10 to 13, wherein the composition is for stress incontinence improvement.
15. The use according to any one of claims 10 to 13, wherein the composition is for improving urination leakage.
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| WO1998023283A1 (en) * | 1996-11-25 | 1998-06-04 | The President And Fellows Of Harvard College | Methods of inhibiting protein degradation to combat muscle wasting |
| JP2016160183A (en) * | 2015-02-27 | 2016-09-05 | 森永乳業株式会社 | Muscular atrophy inhibitor |
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| JPH06256387A (en) * | 1991-06-14 | 1994-09-13 | Suetsuna Yoko | New peptide, its production and hypotensive agent comprising the same as active ingredient |
| US6126939A (en) * | 1996-09-03 | 2000-10-03 | Yeda Research And Development Co. Ltd. | Anti-inflammatory dipeptide and pharmaceutical composition thereof |
| JP2001089387A (en) * | 1999-09-17 | 2001-04-03 | Otsuka Pharmaceut Co Ltd | Muscular atropy inhibitory composition |
| JP2002338464A (en) | 2001-05-14 | 2002-11-27 | Kikkoman Corp | Muscular atrophy inhibitor |
| TWI353252B (en) | 2004-04-28 | 2011-12-01 | Cms Peptides Patent Holding Company Ltd | Biologically active peptide vapeehptllteaplnpk der |
| JP5196708B2 (en) * | 2005-02-04 | 2013-05-15 | 富士化学工業株式会社 | Muscle atrophy improving agent and food and drink comprising astaxanthin and / or ester thereof as active ingredients |
| US20060216279A1 (en) * | 2005-03-22 | 2006-09-28 | Glass David J | Myostatin inhibiting fusion polypeptides and therapeutic methods thereof |
| JP2006328031A (en) | 2005-05-30 | 2006-12-07 | Asahi Breweries Ltd | Muscular fiber type shift inhibitor |
| JP2008013473A (en) | 2006-07-05 | 2008-01-24 | Kao Corp | Muscle hypofunction inhibitor |
| US8962678B2 (en) | 2006-07-05 | 2015-02-24 | Kao Corporation | Senescence inhibitor |
| JP5622593B2 (en) * | 2009-02-02 | 2014-11-12 | 国立大学法人京都大学 | Pharmaceutical or food containing peptide |
| KR101080271B1 (en) | 2009-03-31 | 2011-11-08 | 주식회사 웰스킨 | Ultraviolet-induced reaction controlling cosmetic composition containing dipeptide |
| JP2011184314A (en) * | 2010-03-04 | 2011-09-22 | Snow Brand Milk Products Co Ltd | Muscular atrophy-preventing agent |
| WO2013118773A1 (en) * | 2012-02-06 | 2013-08-15 | 味の素株式会社 | Prophylactic or therapeutic agent for idiopathic inflammatory myopathies |
| KR101533308B1 (en) * | 2012-08-24 | 2015-07-03 | 경희대학교 산학협력단 | Pharmaceutical composition containing Peptide with angiotensin-I Converting Enzyme inhibitory activity for preventing or treating cardiovascular disease |
| JP6222663B2 (en) * | 2012-08-24 | 2017-11-01 | 国立大学法人徳島大学 | Muscle atrophy inhibitor |
| DK3835310T3 (en) | 2012-09-13 | 2024-06-03 | Bristol Myers Squibb Co | FIBRONECTIN-BASED SKELETAL DOMAIN PROTEINS THAT BIND TO MYSTATIN |
| TW201434470A (en) * | 2012-09-24 | 2014-09-16 | Abbott Lab | Nutritional compositions and methods for enhancing cognitive function and muscle function |
| JP2014141462A (en) * | 2012-12-27 | 2014-08-07 | Raffinee International Co Ltd | Peptide, and angiotensin converting enzyme inhibitor, antihypertensive agent, and food and drink product |
| ES2714127T3 (en) | 2013-10-24 | 2019-05-27 | Tokyo Metropolitan Geriatric Hospital And Inst Of Gerontology | Muscle stem cells or myoblasts, screening procedure for substances that participate in metabolic conversion using them, and pharmaceutical composition comprising the substance obtained from said screening procedure |
| JP2016193865A (en) * | 2015-03-31 | 2016-11-17 | キリン株式会社 | Compositions for microglia phagocytosis activity acceleration and prediction method of microglia phagocytosis activity-enhancing action |
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| WO1998023283A1 (en) * | 1996-11-25 | 1998-06-04 | The President And Fellows Of Harvard College | Methods of inhibiting protein degradation to combat muscle wasting |
| JP2016160183A (en) * | 2015-02-27 | 2016-09-05 | 森永乳業株式会社 | Muscular atrophy inhibitor |
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| US11331366B2 (en) | 2022-05-17 |
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| JP7077235B2 (en) | 2022-05-30 |
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